Despite between one- and two-thirds of US men who have sex with men (MSM) acquire HIV from their primary 4 same-sex relationship partner (i.e., male couples), most HIV prevention efforts have targeted MSM at the 5 individual- and community-levels. Substance use is also an important Public Health issue that affects HIV 6 acquisition and transmission among MSM; substances are often used to enhance pleasure and sustain 7 engagement in sexual behaviors including condomless anal sex (CAS). Findings from the few studies 8 conducted with male couples indicate their use of substances with sex negatively impacts their relationship 9 dynamics and behaviors related to HIV prevention, including CAS with casual MSM partners and poor 10 treatment adherence. Although these findings suggest the need to intervene for prevention, less is known 11 about how primary partners within the male couple influence one another's use of substances, the different 12 context(s) in which they use substances, and how their usage directly affects their risk for HIV and dynamics of 13 the relationship. To that calling, we propose to conduct a 4-year mixed method study that is theoretically 14 grounded to examine how male couples' use of substances affects their relationship and risk for acquisition 15 and/or transmission of HIV. We will use venue-time sampling to recruit 225 substance-using male couples, 16 diverse in terms of HIV status and relationship length, from community and Internet venues in South Florida. 17 We will collect qualitative and quantitative longitudinal dyadic data over a 6-month period to examine the 18 associations between intrapersonal, interpersonal and contextual factors in general and with event level 19 substance use. Participants will complete in-person ACASI at 3 time points (baseline, 3 and 6 months), and 20 daily ecological momentary assessments (EMA) during months 2 and 5. Every third reported substance use 21 event will be supplemented with an in-depth phone interview. All data will be collected independently from each 22 partner of the couple, and couples' substance use and HIV serostatus will be verified at baseline, 3 and 6 23 months. Longitudinal quantitative data obtained from the ACASI and EMA will be analyzed using 24 mixed/multilevel models, including actor-partner effects. Qualitative content analysis, specifically latent and 25 manifest content analysis, will be used to identify and describe the major themes and sub-themes that emerge 26 from the phone interview data. We will use standard mixed methodology to integrate the quantitative and 27 qualitative findings to elucidate how primary partners' influence one another's use of substances and risk for 28 HIV, and how their usage affects dynamics of their relationship. Under the direction of Mitchell, he and his 29 team of senior co-investigators will disseminate these findings, and apply them toward development of a 30 couples-focused HIV and substance use preventive intervention for use in a future project.